DOI QR코드

DOI QR Code

Plasma Neutrophil Gelatinase-Associated Lipocalin as a Marker of Tubular Damage in Diabetic Nephropathy

  • Kim, So Young (Department of Laboratory Medicine, LabGenomics Clinical Laboratory) ;
  • Jeong, Tae-Dong (Department of Laboratory Medicine, College of Medicine, Ewha Womans University) ;
  • Lee, Woochang (Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center) ;
  • Chun, Sail (Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center) ;
  • Sunwoo, Sung (Department of Family Medicine, University of Ulsan College of Medicine and Asan Medical Center) ;
  • Kim, Soon Bae (Department of Internal Medicine, University of Ulsan College of Medicine and Asan Medical Center) ;
  • Min, Won-Ki (Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center)
  • Received : 2017.07.28
  • Accepted : 2018.05.25
  • Published : 2018.11.01

Abstract

Background: An increase in neutrophil gelatinase-associated lipocalin (NGAL) indicates tubular injury. Diabetic nephropathy causes typical changes in the kidney, characterized by glomerulosclerosis and eventual tubular damage. We validated the usefulness of plasma NGAL (pNGAL) as a biomarker of tubular damage in patients with diabetic nephropathy. Methods: We included 376 patients with diabetes mellitus (260 patients with chronic renal insufficiency who had not received hemodialysis and 116 hemodialyzed due to diabetic nephropathy) and 24 healthy controls. Patients with chronic renal insufficiency were divided into three groups according to urinary albumin excretion (UAE) levels. pNGAL levels were measured using the Triage NGAL test (Alere, San Diego, CA, USA) and were compared between groups. We also examined whether pNGAL level was related to the degree of albuminuria and cystatin C-based glomerular filtration rate (GFR). Results: Mean pNGAL levels of the healthy controls, chronic renal insufficiency patients with diabetes mellitus, and hemodialyzed patients were $61.9{\pm}5.3ng/mL$, $93.4{\pm}71.8ng/mL$, and $1,536.9{\pm}554.9ng/mL$, respectively. pNGAL level increased significantly in patients with severe albuminuria (P <0.001) and had a moderate correlation with the degree of albuminuria (r=0.467; P <0.001) and GFR (r=0.519; P <0.001). Multivariate regression analysis showed that the pNGAL level was associated with tubular damage independent of patient age, sex, and GFR. Conclusions: pNGAL level independently reflects the degree of tubular damage in patients with diabetic nephropathy. Measurement of pNGAL, combined with UAE, would enable simultaneous, highly reliable assessments of tubular damage for such patients.

Keywords

References

  1. Devarajan P. NGAL in acute kidney injury: from serendipity to utility. Am J Kidney Dis 2008;52:395-9. https://doi.org/10.1053/j.ajkd.2008.07.008
  2. Bolignano D, Coppolino G, Romeo A, De Paola L, Buemi A, Lacquaniti A, et al. Neutrophil gelatinase-associated lipocalin (NGAL) reflects iron status in haemodialysis patients. Nephrol Dial Transplant 2009;24:3398-403. https://doi.org/10.1093/ndt/gfp310
  3. Gilbert RE and Cooper ME. The tubulointerstitium in progressive diabetic kidney disease: more than an aftermath of glomerular injury? Kidney Int 1999;56:1627-37. https://doi.org/10.1046/j.1523-1755.1999.00721.x
  4. Nielsen SE, Andersen S, Zdunek D, Hess G, Parving HH, Rossing P. Tubular markers do not predict the decline in glomerular filtration rate in type 1 diabetic patients with overt nephropathy. Kidney Int 2011;79: 1113-8. https://doi.org/10.1038/ki.2010.554
  5. Nielsen SE, Schjoedt KJ, Astrup AS, Tarnow L, Lajer M, Hansen PR, et al. Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM1) in patients with diabetic nephropathy: a cross-sectional study and the effects of lisinopril. Diabet Med 2010;27:1144-50. https://doi.org/10.1111/j.1464-5491.2010.03083.x
  6. Finne P, Reunanen A, Stenman S, Groop PH, Gronhagen-Riska C. Incidence of end-stage renal disease in patients with type 1 diabetes. JAMA 2005;294:1782-7. https://doi.org/10.1001/jama.294.14.1782
  7. Bolignano D, Lacquaniti A, Coppolino G, Donato V, Fazio MR, Nicocia G, et al. Neutrophil gelatinase-associated lipocalin as an early biomarker of nephropathy in diabetic patients. Kidney Blood Press Res 2009;32:91-8. https://doi.org/10.1159/000209379
  8. Nielsen SE, Hansen HP, Jensen BR, Parving HH, Rossing P. Urinary neutrophil gelatinase-associated lipocalin and progression of diabetic nephropathy in type 1 diabetic patients in a four-year follow-up study. Nephron Clin Pract 2011;118:c130-5. https://doi.org/10.1159/000320615
  9. Bolignano D, Lacquaniti A, Coppolino G, Donato V, Campo S, Fazio MR, et al. Neutrophil gelatinase-associated lipocalin (NGAL) and progression of chronic kidney disease. Clin J Am Soc Nephrol 2009;4:337-44. https://doi.org/10.2215/CJN.03530708
  10. Phillips AO. The role of renal proximal tubular cells in diabetic nephropathy. Curr Diab Rep 2003;3:491-6. https://doi.org/10.1007/s11892-003-0013-1
  11. Di Somma S, Magrini L, De Beradinis B, Marino R, Ferri E, Moscatelli P, et al. Additive value of blood neutrophil gelatinase-associated lipocalin to clinical judgement in acute kidney injury diagnosis and mortality prediction in patients hospitalized from the emergency department. Crit Care 2013;17:R29. https://doi.org/10.1186/cc12510
  12. Hur M, Kim H, Lee S, Cristofano F, Magrini L, Marino R, et al. Diagnostic and prognostic utilities of multimarkers approach using procalcitonin, B-type natriuretic peptide, and neutrophil gelatinase-associated lipocalin in critically ill patients with suspected sepsis. BMC Infect Dis 2014;14:224. https://doi.org/10.1186/1471-2334-14-224
  13. Kim H, Hur M, Lee S, Marino R, Magrini L, Cardelli P, et al. Proenkephalin, neutrophil gelatinase-associated lipocalin, and estimated glomerular filtration rates in patients with sepsis. Ann Lab Med 2017;37:388-97. https://doi.org/10.3343/alm.2017.37.5.388
  14. Malyszko J, Malyszko JS, Koc-Zorawska E, Kozminski P, Mysliwiec M. Neutrophil gelatinase-associated lipocalin in dialyzed patients is related to residual renal function, type of renal replacement therapy and inflammation. Kidney Blood Press Res 2009;32:464-9. https://doi.org/10.1159/000274048
  15. Musial K and Zwolinska D. Neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinases as novel stress markers in children and young adults on chronic dialysis. Cell Stress Chaperones 2011;16:163-71. https://doi.org/10.1007/s12192-010-0228-4
  16. Bolignano D, Coppolino G, Romeo A, Lacquaniti A, Buemi M. Neutrophil gelatinase-associated lipocalin levels in chronic haemodialysis patients. Nephrology (Carlton) 2010;15:23-6.
  17. Kusaka M, Kuroyanagi Y, Mori T, Nagaoka K, Sasaki H, Maruyama T, et al. Serum neutrophil gelatinase-associated lipocalin as a predictor of organ recovery from delayed graft function after kidney transplantation from donors after cardiac death. Cell Transplant 2008;17:129-34. https://doi.org/10.3727/000000008783907116

Cited by

  1. Urinary Biomarkers may Complement the Cleveland Score for Prediction of Adverse Kidney Events After Cardiac Surgery: A Pilot Study vol.40, pp.2, 2020, https://doi.org/10.3343/alm.2020.40.2.131
  2. Current updates on protein as biomarkers for diabetic kidney disease: a systematic review vol.12, pp.None, 2018, https://doi.org/10.1177/20420188211049612
  3. Biomarker-Guided Risk Assessment for Acute Kidney Injury: Time for Clinical Implementation? vol.41, pp.1, 2018, https://doi.org/10.3343/alm.2021.41.1.1
  4. Effectiveness of Plasma and Urine Neutrophil Gelatinase-Associated Lipocalin for Predicting Acute Kidney Injury in High-Risk Patients vol.41, pp.1, 2018, https://doi.org/10.3343/alm.2021.41.1.60
  5. Dendrobium Mixture Ameliorates Diabetic Nephropathy in db/db Mice by Regulating the TGF-β1/Smads Signaling Pathway vol.2021, pp.None, 2018, https://doi.org/10.1155/2021/9931983